Studies on the psychopharmacological activities of Rumex nepalensis Spreng. root extract in rats and mice.

The methanol extract of Rumex nepalensis Spreng. (Family - Polygonaceae) was assessed for different psychopharmacological activities in rats and mice by evaluation of general behaviour, exploratory behaviour, muscle relaxant activity and phenobarbitone sodium-induced sleeping time. The extract at doses 200 mg/kg and above exhibited a reduction in spontaneous activity (general behavioural profile), a decrease in exploratory behavioural pattern in the Y-maze and Head-dip tests, a reduction in muscle relaxant activity in rotarod, 30 degrees inclined screen and traction tests, and also potentiated phenobarbitone sodium-induced sleeping time.     

Ameliorative potential of montelukast on ischemia-reperfusion injury induced vasculitic neuropathic pain in rat

AimsIschemia -reperfusion (I/R) event in vascular and nervous system has been documented to rising ischemic and vasculitic neuropathic pain, clinically resembles the complex regional pain syndrome (CRPS). The present study evaluated the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC₄ and Cys-LTD₄) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic pain in rats.Main MethodsBehavioral parameters were assessed at different time intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic nerve tissue samples were also performed along with histopathological studies.Key FindingsBehavioral pain assessment has shown increase in paw and tail withdrawal threshold in montelukast treated groups against thermal and mechanical stimuli as compared to I/R control group. We observed a decrease in the total calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO) activity levels, whereas there is rise in reduced glutathione level in montelukast treated groups as compared to I/R control group. However, significant behavioral and biochemical results were observed only in medium and high dose of treated groups which were comparable to normal control group. Moreover, histopathological study has revealed the reduction of I/R induced neuronal edema and axonal degeneration due to montelukast.SignificanceMontelukast has ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to inhibition of lipid peroxidation, reduction of oxidative stress, release of inflammatory mediators and neuroprotective actions. Hence, it could be used as a novel therapeutic agent for the management of vasculitic inflammation related neuropathic pain.     

DNA repair genes hOGG1, XRCC1 and ERCC2 polymorphisms and their molecular mapping in breast cancer patients from India

Molecular Biology Reports - Identification of modifier genes predisposing to breast cancer (BC) phenotype remains a significant challenge and varies with ethnicity. The genetic variability observed...     

Discovery of BMS-961955, an allosteric inhibitor of the hepatitis C virus NS5B polymerase

The synthesis, structure-activity relationship (SAR) data, and further optimization of the metabolic stability and pharmacokinetic (PK) properties for a previously disclosed class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors are described. These efforts led to the discovery of BMS-961955 as a viable contingency backup to beclabuvir which was recently approved in Japan for the treatment of HCV as part of a three drug, single pill combination marketed as Ximency^TM.     

Simultaneous off-pump coronary artery bypass grafting and ascending aortobifemoral bypass graft via ventral abdominal route

Aortoiliac disease often coexists with coronary artery disease. It is not uncommon to subject a patient to two separate interventions. We report two cases in which in simultaneous off-pump coronary artery bypass grafting was done with an ascending aortobifemoral bypass graft through the ventral abdominal route without any additional morbidity. Combining a technically simple method of limb bypass with an off-pump cardiac surgery is a promising procedure for revascularization of myocardium and lower limbs. We discuss the merits of combining an off-pump coronary artery bypass grafting procedure with a limb bypass.     

Exploring conformational space using a mean field technique with MOLS sampling

The computational identification of all the low energy structures of a peptide given only its sequence is not an easy task even for small peptides,due to the multiple-minima problem and combinatorial explosion. We have developed an algorithm, called the MOLS technique,that addresses this problem, and have applied it to a number of different aspects of the study of peptide and protein structure. Conformational studies of oligopeptides, including loop sequences in proteins have been carried out using this technique. In general the calculations identified all the folds determined by previous studies,and in addition picked up other energetically favorable structures. The method was also used to map the energy surface of the peptides. In another application, we have combined the MOLS technique, using it to generate a library of low energy structures of an oligopeptide, with a genetic algorithm to predict protein structures. The method has also been applied to explore the conformational space of loops in protein structures.Further, it has been applied to the problem of docking a ligand in its receptor site, with encouraging results.